This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our laboratory carries out structural studies of molecules involved in our adaptive and innate immune systems. These molecules include antibodies, T cell receptors, major histocompatibility complex molecules, CD1 molecules and Toll-like receptors, as well as their cellular co-factors. We have an extensive program studying neutralizing antibodies against the HIV-1 virus and the influenza virus, and will be studying complexes of these antibodies with their viral antigens gp120 and gp41 (from HIV-1) and hemagglutinin and neuraminidase (from influenza). In addition, we are interested in the evolution of the immune system and are studying immune receptors from shark and lamprey in order to see how they compare to their mammalian counterparts. Many of the proteins we are studying are glycoproteins that tend to diffract weakly, so the use of synchrotron radiation is critical for their structure determinations. In addition to the immune-system related work, we are studying the enzymes GAR transformylase and AICAR transformylase, in complex with inhibitors, in a program of anti-cancer structure-based drug design and also human transthyretin in complex with anti-amyloidosis inhibitors.